Despite the prompt use of advances in medical and surgical treatment of theoretically reversible heart disease in infants and young children, the mortality in the first three months of life remains distressingly high. In clinical settings, we find relative unresponsiveness of neonatal patients to certain cardioactive drugs which lends credence to the few acute animal studies that suggest a difference in pharmacologic response of the immature compared to the mature cardiovascular system. In this study, we propose to use a chronically instrumented unanesthetized puppy model to investigate several components of cardiovascular function by testing the response of the preparations at different ages to (1) adrenergic agonists, (2) adrenergic antagonists, (3) prostaglandin synthetase inhibitors, and (4) inotropic and vasodilator drugs. The indices of cardiovascular function to be studied include the velocity of aortic and renal artery blood flow, phasic and mean blood pressure in the aorta, left atrium, and right atrium. Changes in systemic vascular resistance and stroke work index will be calculated. We will determine if there is developmental variation of the number of myocardial beta-receptors per gram of protein, affinity of myocardial beta-receptors for agonists and antagonists, and coupling of the beta-receptor to adenylate cyclase activity. We hope to develop an expandable range-gated pulsed ultrasonic Doppler flow probe that accomodates growth of the vessel. Knowledge of age-related variability of response of the cardiovascular system to drugs will allow more effective treatment of children with cardiovascular disease. A refined pulsed ultrasonic Doppler flow probe may be appliable to the measurement of cardiac function following cardiovascular operative procedures in young children.